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Published on: January 22, 2019
Membrane lipid composition and rapid endocytic retrieval modulate Wingless secretion
Ines Alvarez-Rodrigo1, David Willnow2, Cyrille Alexandre2
1The Francis Crick Institute, London, UK. ines.alvarezrodrigo@crick.ac.uk.
Wingless secretion relies on Wntless cargo receptor and rapid endocytosis to prevent aggregation. Membrane lipid composition influences Wingless stability and release, ensuring proper basolateral secretion.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Wnt family ligands are crucial signaling molecules.
- These ligands possess a lipid moiety requiring protection from aqueous environments.
- Wntless acts as a cargo receptor facilitating Wnt secretion.
Purpose of the Study:
- To elucidate the mechanism of Wingless (Wnt) secretion.
- To investigate the role of endocytosis and lipid composition in Wnt trafficking.
- To understand how Wingless avoids aggregation during secretion.
Main Methods:
- Acute endocytosis inhibition experiments.
- Super-resolution microscopy.
- Analysis of Wingless aggregation and solubilization using lipid-binding proteins and liposomes.
Main Results:
- Wingless dissociates from Wntless at the apical membrane but is retained by endocytosis.
- Wingless traffics independently of Wntless through Rab7/Rab4-positive endosomes for basolateral release.
- Inhibition of endocytosis or ceramide synthase leads to apical release in punctate structures, suggesting aggregation.
Conclusions:
- Rapid endocytosis is essential for preventing Wingless aggregation and ensuring orderly secretion.
- Membrane lipid composition may regulate Wntless-Wingless complex stability and Wingless lipid accommodation.
- These processes collectively ensure efficient basolateral secretion of Wnt ligands.
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